Interpretive Summary: Currently 15% of U.S. infants are fed soy formulas containing isoflavones, but little is known of the effect of these phytochemicals on developing infants. This research focuses on the evaluation of the effect of the soy isoflavone genistein on intestinal development in piglets. A sow milk replacement with no isoflavone, a low level of isoflavone, and a high level of isoflavones were fed to piglets for 10 days. Formula uptake, weight gain, and intestinal length and weight were the same for all groups. The isoflavone had no effect on several parameters measured in the intestines, but the isoflavone decreased certain intestinal cell type proliferation and migration. This indicates that soy isoflavones do slow the proliferation of new intestinal cells, but have little effect on the differentiation of the cell types.

Technical Abstract:
Currently 15% of U.S. infants are fed soy formulas containing up to 14 mg genistein equivalents/L. Our goal was to investigate the impact of dietary genistein on intestinal development. Piglets (n=8/group) were fed sow milk replacer (MR), MR + 1 mg/L genistein (LG), or MR + 14 mg/L genistein (HG) for 10 days. Formula intake, weight gain, and intestinal length and weight were similar in all groups. Average serum genistein concentration in the HG group was similar to that of soy formula fed infants. No significant effects of genistein on enterocyte apoptosis, lactase and sucrase activities, or electrophysiological measures were observed in jejunum or ileum. Jejunal and ileal villus heights were not significantly different, but the percentage of PCNA positive jejunal crypt cells in the HG was reduced 50% compared to than MR. and LG (p=0.001), indicating decreased proliferation. Enterocyte migration distance in the HG group tended to be 20% less (p=0.1) than LG or MR. Jejunal estrogen receptor (ER) beta mRNA expression in HG was half of that in LG (p=0.05), but neither was significantly different from MR. In conclusion, genistein at the level present in soy infant formula is bioactive in the small intestine and results in reduced enterocyte proliferation and migration. The lack of effect of genistein on nutrient transport and enzyme activity suggests that the impact of genistein is greater on proliferating vs. differentiated intestinal cells.